XPP1_HUMAN
ID XPP1_HUMAN Reviewed; 623 AA.
AC Q9NQW7; A8K071; G5E9Y2; G8JLB2; O15250; Q53EX6; Q8N3Q0; Q96D23;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Xaa-Pro aminopeptidase 1;
DE EC=3.4.11.9;
DE AltName: Full=Aminoacylproline aminopeptidase;
DE AltName: Full=Cytosolic aminopeptidase P;
DE AltName: Full=Soluble aminopeptidase P;
DE Short=sAmp;
DE AltName: Full=X-Pro aminopeptidase 1;
DE AltName: Full=X-prolyl aminopeptidase 1, soluble;
GN Name=XPNPEP1 {ECO:0000312|EMBL:AAH05126.1};
GN Synonyms=XPNPEPL {ECO:0000312|EMBL:CAA65068.1}, XPNPEPL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAA65068.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=9465902; DOI=10.1159/000134671;
RA Vanhoof G., Goossens F., Juliano M.A., Juliano L., Hendriks D.,
RA Schatteman K., Lin A.H., Scharpe S.;
RT "Isolation and sequence analysis of a human cDNA clone (XPNPEPL) homologous
RT to X-prolyl aminopeptidase (aminopeptidase P).";
RL Cytogenet. Cell Genet. 78:275-280(1997).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAF97866.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10871044; DOI=10.1006/abbi.2000.1792;
RA Sprinkle T.J., Caldwell C., Ryan J.W.;
RT "Cloning, chromosomal sublocalization of the human soluble aminopeptidase P
RT gene (XPNPEP1) to 10q25.3 and conservation of the putative proton shuttle
RT and metal ligand binding sites with XPNPEP2.";
RL Arch. Biochem. Biophys. 378:51-56(2000).
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAF75795.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC TISSUE=Pancreatic adenocarcinoma {ECO:0000269|PubMed:11106490};
RX PubMed=11106490; DOI=10.1021/bi001585c;
RA Cottrell G.S., Hooper N.M., Turner A.J.;
RT "Cloning, expression, and characterization of human cytosolic
RT aminopeptidase P: a single manganese(II)-dependent enzyme.";
RL Biochemistry 39:15121-15128(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5] {ECO:0000305, ECO:0000312|EMBL:CAD38640.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305, ECO:0000312|EMBL:CAD38640.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8] {ECO:0000305, ECO:0000312|EMBL:AL354951}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9] {ECO:0000305, ECO:0000312|EMBL:CAD38640.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10] {ECO:0000305, ECO:0000312|EMBL:AAH05126.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon {ECO:0000312|EMBL:AAH13417.4},
RC Ovary {ECO:0000312|EMBL:AAH05126.1}, and
RC Placenta {ECO:0000312|EMBL:AAH07579.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11] {ECO:0000305}
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Platelet {ECO:0000269|PubMed:12665801};
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS,
RP COFACTOR, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP GLU-41 AND TRP-477, AND SUBUNIT.
RX PubMed=18515364; DOI=10.1074/jbc.m710274200;
RA Li X., Lou Z., Li X., Zhou W., Ma M., Cao Y., Geng Y., Bartlam M.,
RA Zhang X.C., Rao Z.;
RT "Structure of human cytosolic X-prolyl aminopeptidase: a double Mn(II)-
RT dependent dimeric enzyme with a novel three-domain subunit.";
RL J. Biol. Chem. 283:22858-22866(2008).
CC -!- FUNCTION: Contributes to the degradation of bradykinin. Catalyzes the
CC removal of a penultimate prolyl residue from the N-termini of peptides,
CC such as Arg-Pro-Pro.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of any N-terminal amino acid, including proline, that
CC is linked to proline, even from a dipeptide or tripeptide.;
CC EC=3.4.11.9; Evidence={ECO:0000269|PubMed:11106490,
CC ECO:0000269|PubMed:18515364};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11106490, ECO:0000269|PubMed:18515364};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:11106490,
CC ECO:0000269|PubMed:18515364};
CC -!- ACTIVITY REGULATION: Inhibited by apstatin and the metal ion chelators
CC EDTA and 1,10-phenanthroline. Partially inhibited by dithiothreitol.
CC Not inhibited by enalaprilat or amastatin.
CC {ECO:0000269|PubMed:11106490}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100.6 uM for bradykinin {ECO:0000269|PubMed:11106490,
CC ECO:0000269|PubMed:18515364};
CC KM=308 uM for the tripeptide Arg-Pro-Pro
CC {ECO:0000269|PubMed:11106490, ECO:0000269|PubMed:18515364};
CC pH dependence:
CC Optimum pH is 8.2. {ECO:0000269|PubMed:11106490,
CC ECO:0000269|PubMed:18515364};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11106490,
CC ECO:0000269|PubMed:18515364}.
CC -!- INTERACTION:
CC Q9NQW7-3; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-12079490, EBI-742054;
CC Q9NQW7-3; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-12079490, EBI-739467;
CC Q9NQW7-3; P69892: HBG2; NbExp=3; IntAct=EBI-12079490, EBI-3910089;
CC Q9NQW7-3; Q15669: RHOH; NbExp=3; IntAct=EBI-12079490, EBI-1244971;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1 {ECO:0000269|PubMed:9465902};
CC IsoId=Q9NQW7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQW7-2; Sequence=VSP_051752;
CC Name=3;
CC IsoId=Q9NQW7-3; Sequence=VSP_045250;
CC Name=4;
CC IsoId=Q9NQW7-4; Sequence=VSP_045250, VSP_051752;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, including
CC pancreas, heart, muscle, kidney, liver, lung and brain. Highest levels
CC in pancreas. {ECO:0000269|PubMed:9465902}.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD38640.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X95762; CAA65068.1; -; mRNA.
DR EMBL; AF195530; AAF97866.1; -; mRNA.
DR EMBL; AF272981; AAF75795.1; -; mRNA.
DR EMBL; AK289436; BAF82125.1; -; mRNA.
DR EMBL; CR456922; CAG33203.1; -; mRNA.
DR EMBL; AK223513; BAD97233.1; -; mRNA.
DR EMBL; AL833411; CAD38640.1; ALT_INIT; mRNA.
DR EMBL; AL354951; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49577.1; -; Genomic_DNA.
DR EMBL; BC005126; AAH05126.1; -; mRNA.
DR EMBL; BC007579; AAH07579.1; -; mRNA.
DR EMBL; BC013417; AAH13417.4; -; mRNA.
DR CCDS; CCDS53576.1; -. [Q9NQW7-4]
DR CCDS; CCDS7560.2; -. [Q9NQW7-3]
DR RefSeq; NP_001161076.1; NM_001167604.1. [Q9NQW7-4]
DR RefSeq; NP_001311061.1; NM_001324132.1. [Q9NQW7-1]
DR RefSeq; NP_065116.3; NM_020383.3. [Q9NQW7-3]
DR PDB; 3CTZ; X-ray; 1.60 A; A=1-623.
DR PDBsum; 3CTZ; -.
DR AlphaFoldDB; Q9NQW7; -.
DR SMR; Q9NQW7; -.
DR BioGRID; 113346; 93.
DR IntAct; Q9NQW7; 17.
DR MINT; Q9NQW7; -.
DR STRING; 9606.ENSP00000421566; -.
DR BindingDB; Q9NQW7; -.
DR ChEMBL; CHEMBL3782; -.
DR GuidetoPHARMACOLOGY; 1578; -.
DR MEROPS; M24.009; -.
DR GlyGen; Q9NQW7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQW7; -.
DR MetOSite; Q9NQW7; -.
DR PhosphoSitePlus; Q9NQW7; -.
DR BioMuta; XPNPEP1; -.
DR DMDM; 68566146; -.
DR CPTAC; CPTAC-694; -.
DR CPTAC; CPTAC-695; -.
DR EPD; Q9NQW7; -.
DR jPOST; Q9NQW7; -.
DR MassIVE; Q9NQW7; -.
DR MaxQB; Q9NQW7; -.
DR PaxDb; Q9NQW7; -.
DR PeptideAtlas; Q9NQW7; -.
DR PRIDE; Q9NQW7; -.
DR ProteomicsDB; 34080; -.
DR ProteomicsDB; 34174; -.
DR ProteomicsDB; 82211; -. [Q9NQW7-1]
DR ProteomicsDB; 82212; -. [Q9NQW7-2]
DR ABCD; Q9NQW7; 2 sequenced antibodies.
DR Antibodypedia; 31645; 198 antibodies from 34 providers.
DR DNASU; 7511; -.
DR Ensembl; ENST00000322238.12; ENSP00000324011.8; ENSG00000108039.18. [Q9NQW7-4]
DR Ensembl; ENST00000502935.6; ENSP00000421566.1; ENSG00000108039.18. [Q9NQW7-3]
DR GeneID; 7511; -.
DR KEGG; hsa:7511; -.
DR MANE-Select; ENST00000502935.6; ENSP00000421566.1; NM_020383.4; NP_065116.3. [Q9NQW7-3]
DR UCSC; uc001kyp.2; human. [Q9NQW7-1]
DR CTD; 7511; -.
DR DisGeNET; 7511; -.
DR GeneCards; XPNPEP1; -.
DR HGNC; HGNC:12822; XPNPEP1.
DR HPA; ENSG00000108039; Low tissue specificity.
DR MIM; 602443; gene.
DR neXtProt; NX_Q9NQW7; -.
DR OpenTargets; ENSG00000108039; -.
DR PharmGKB; PA37415; -.
DR VEuPathDB; HostDB:ENSG00000108039; -.
DR eggNOG; KOG2413; Eukaryota.
DR GeneTree; ENSGT00940000157716; -.
DR HOGENOM; CLU_011781_2_2_1; -.
DR InParanoid; Q9NQW7; -.
DR OMA; YRPGKWG; -.
DR OrthoDB; 417805at2759; -.
DR PhylomeDB; Q9NQW7; -.
DR TreeFam; TF314183; -.
DR BRENDA; 3.1.8.1; 2681.
DR BRENDA; 3.4.11.9; 2681.
DR PathwayCommons; Q9NQW7; -.
DR SABIO-RK; Q9NQW7; -.
DR SignaLink; Q9NQW7; -.
DR BioGRID-ORCS; 7511; 23 hits in 1082 CRISPR screens.
DR ChiTaRS; XPNPEP1; human.
DR EvolutionaryTrace; Q9NQW7; -.
DR GeneWiki; XPNPEP1; -.
DR GenomeRNAi; 7511; -.
DR Pharos; Q9NQW7; Tchem.
DR PRO; PR:Q9NQW7; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9NQW7; protein.
DR Bgee; ENSG00000108039; Expressed in body of pancreas and 205 other tissues.
DR ExpressionAtlas; Q9NQW7; baseline and differential.
DR Genevisible; Q9NQW7; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0010815; P:bradykinin catabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd01085; APP; 1.
DR Gene3D; 3.40.350.10; -; 2.
DR Gene3D; 3.90.230.10; -; 1.
DR InterPro; IPR029149; Creatin/AminoP/Spt16_NTD.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000587; Creatinase_N.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR033740; Pept_M24B.
DR InterPro; IPR032416; Peptidase_M24_C.
DR InterPro; IPR001131; Peptidase_M24B_aminopep-P_CS.
DR Pfam; PF01321; Creatinase_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR Pfam; PF16188; Peptidase_M24_C; 1.
DR SUPFAM; SSF53092; SSF53092; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR PROSITE; PS00491; PROLINE_PEPTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Aminopeptidase; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Manganese; Metal-binding;
KW Metalloprotease; Protease; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801"
FT CHAIN 2..623
FT /note="Xaa-Pro aminopeptidase 1"
FT /id="PRO_0000185083"
FT BINDING 77
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 395
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 415
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT BINDING 426
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT BINDING 426
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT BINDING 489
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT BINDING 489
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 498
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 523
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT BINDING 523
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O44750"
FT BINDING 537
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT BINDING 537
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:18515364,
FT ECO:0007744|PDB:3CTZ"
FT MOD_RES 304
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1
FT /note="M -> MAASRKPPRVRVNHQDFQLRNLRIIEPNEVTHSGDTGVETDGRM
FT (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045250"
FT VAR_SEQ 398..421
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_051752"
FT MUTAGEN 41
FT /note="E->A: Reduces activity by 10%."
FT /evidence="ECO:0000269|PubMed:18515364"
FT MUTAGEN 477
FT /note="W->E: Interferes with dimerization and reduces
FT activity by 94%."
FT /evidence="ECO:0000269|PubMed:18515364"
FT CONFLICT 90
FT /note="W -> C (in Ref. 10; AAH13417)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="K -> R (in Ref. 4; BAF82125)"
FT /evidence="ECO:0000305"
FT CONFLICT 332
FT /note="R -> P (in Ref. 1; CAA65068 and 2; AAF97866)"
FT /evidence="ECO:0000305"
FT CONFLICT 496
FT /note="N -> D (in Ref. 7; BAD97233)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="H -> R (in Ref. 7; BAD97233)"
FT /evidence="ECO:0000305"
FT CONFLICT 572
FT /note="I -> T (in Ref. 4; BAF82125)"
FT /evidence="ECO:0000305"
FT HELIX 7..16
FT /evidence="ECO:0007829|PDB:3CTZ"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 28..32
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 49..54
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 70..74
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 79..85
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 103..110
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 126..138
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 150..154
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 171..174
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 178..190
FT /evidence="ECO:0007829|PDB:3CTZ"
FT TURN 191..193
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 233..236
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 240..243
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 245..250
FT /evidence="ECO:0007829|PDB:3CTZ"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 263..266
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 296..301
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 307..312
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 314..320
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 324..351
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 359..371
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 376..381
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 388..392
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 400..402
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 412..416
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 427..431
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 438..455
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 465..472
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 474..478
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 487..490
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 493..495
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 519..522
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 525..528
FT /evidence="ECO:0007829|PDB:3CTZ"
FT TURN 529..531
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 532..535
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 537..545
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:3CTZ"
FT STRAND 556..561
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 569..571
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 579..602
FT /evidence="ECO:0007829|PDB:3CTZ"
FT HELIX 606..614
FT /evidence="ECO:0007829|PDB:3CTZ"
SQ SEQUENCE 623 AA; 69918 MW; DF4F5AF41E2F3876 CRC64;
MPPKVTSELL RQLRQAMRNS EYVTEPIQAY IIPSGDAHQS EYIAPCDCRR AFVSGFDGSA
GTAIITEEHA AMWTDGRYFL QAAKQMDSNW TLMKMGLKDT PTQEDWLVSV LPEGSRVGVD
PLIIPTDYWK KMAKVLRSAG HHLIPVKENL VDKIWTDRPE RPCKPLLTLG LDYTGISWKD
KVADLRLKMA ERNVMWFVVT ALDEIAWLFN LRGSDVEHNP VFFSYAIIGL ETIMLFIDGD
RIDAPSVKEH LLLDLGLEAE YRIQVHPYKS ILSELKALCA DLSPREKVWV SDKASYAVSE
TIPKDHRCCM PYTPICIAKA VKNSAESEGM RRAHIKDAVA LCELFNWLEK EVPKGGVTEI
SAADKAEEFR RQQADFVDLS FPTISSTGPN GAIIHYAPVP ETNRTLSLDE VYLIDSGAQY
KDGTTDVTRT MHFGTPTAYE KECFTYVLKG HIAVSAAVFP TGTKGHLLDS FARSALWDSG
LDYLHGTGHG VGSFLNVHEG PCGISYKTFS DEPLEAGMIV TDEPGYYEDG AFGIRIENVV
LVVPVKTKYN FNNRGSLTFE PLTLVPIQTK MIDVDSLTDK ECDWLNNYHL TCRDVIGKEL
QKQGRQEALE WLIRETQPIS KQH
